PB1879: EFFICACY AND SAFETY OF CPX-351 COMPARED TO STANDARD OF CARE CHEMOTHERAPY IN A REAL-LIFE SETTING: SUPPORTING PREVIOUS EVIDENCE AND FACING NEW CHALLENGES
Authors: Beatrice Manghisi, Sara Alberti, Alessia Ripamonti, Paola Perfetti, Lorenza Maria Borin, Monica Fumagalli, Carlo Gambacorti Passerini
Journal: HemaSphere (2023)

Topic: 4. Acute myeloid leukemia - Clinical Background: Acute myeloid leukemia “myelodysplasia-related” and “post-cytotoxic therapies”, as defined by 2022 WHO classification, previously named AML-MRC and therapy-related AML, represent very high-risk subgroups of AML with adverse biological features. CPX-351, a liposomal formulation of cytarabine/daunorubicin, represents a relevant innovation in the treatment of this AML subtype: a significant increase in OS without toxicity excess, compared to SOC, was reported in phase 3 study by Lancet et al. Currently, the setting of real-world experience is under investigation, providing crucial data confirmation. Moreover, increasing knowledge in disease biology led to relevant changes in the diagnostic criteria of MR-AML, opening up to new questions and challenges. Aims: Aim of the study is to compare CPX-351 and SOC chemotherapy in the treatment of AML-MRC and t-AML, in the real-world setting of San Gerardo Hospital in Monza, Italy. Methods: This is a monocentric, observational, retrospective-prospective study with a historical comparison cohort. 24 patients with a new diagnosis of AML-MRC or t-AML in 2015-2022 were enrolled, 13 in CPX-351 cohort and 11 in SOC cohort; median age was 54 years. Primary endpoint was OS; secondary endpoints explored efficacy, safety and HSCT outcomes. As the study was designed before publication of 2022 WHO version, diagnoses were based on 2016 WHO criteria. Results: With a median follow up of 21.2 months, CPX-351 showed a trend towards better OS (not reached vs 15.4 months, p = 0.6) and lower disease-related mortality (25.0% vs 83.3%), compared to SOC. CPX-351 was associated with slower hematologic recovery (median time to ANC > 500/mmc 35 vs 23 days, median time to PLT > 50000/mmc 32 vs 23 days). Despite higher rates of adverse events in CPX-351 cohort (69.6% vs 30.4%), no significant increase in severe infectious AEs or in early mortality was observed. CR/CRi rates at end of treatment were higher in CPX-351 group (92.3% vs 72.3%), despite not meeting statistical significance (p = 0.3). CPX-351 showed lower relapse rates (7.7% vs 36.4%, p= 0.1) and higher rates of HSCT in CR/CRi (91.7% vs 81.3%). In CPX-351 cohort, patients were screened for WT-1 hyperexpression: 7/13 patients, showing hyperexpression, underwent MRD monitoring with WT-1. 6/7 patients obtained MRD negativity after 1st induction, while 1 patient reached MRD negativity after HSCT. We reviewed our MRC-AML diagnoses according to 2022 WHO criteria: 3/24 patients showed only morphologic dysplasia and wouldn’t meet current criteria. Considering MR-AML-defining somatic mutations introduced by 2022 WHO, we identified U2AF1 in 1/24 patients and ASXL1 in 3/24 patients; only 1 patient displayed TP53 mutation in NGS. Summary/Conclusion: Our real-life study, despite small sample size, proved CPX-351 to be safe and effective in 1st line treatment of MRC-AML and t-AML, confirming previous data. The evidence of longer neutropenia in CPX-351 arm, without an increase in serious infections, suggests that liposomal formulation leads to selective marrow toxicity with low mucosal damage and bacterial translocation. As real-life experience with CPX-351 is spreading, new issues need to be addressed. MRD monitoring is crucial in the setting of high-risk AML: WT-1, together with flow-cytometry, is a promising tool in the absence of more reliable molecular markers. New WHO criteria outline the importance of molecular biology in defining MR-AML: further research is needed to identify biological subgroups that would benefit from CPX-351 and selected categories, such as complex-kariotype and TP53+, eligible to biological therapies.Keywords: Therapy-related AML, Real world data, MDS/AML, WT1